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Submitted on December 31, 2002
Accepted on May 12, 2003
2-Adrenergic Receptor Overexpression
1 Baker Heart Research Institute and Alfred Heart Centre, Alfred Hospital, Melbourne, Victoria, Australia
* To whom correspondence should be addressed. E-mail: xiaojun.du{at}baker.edu.au.
Sex differences in cardiomyopathic phenotype and the role of gonadal status were studied in mice with cardiac overexpression of 
2-adrenergic receptors (AR) over 6-15 months of age. Survival to 15 months was 96% in wild-type mice, but was poorer in transgenic (TG) mice and lower for males than females (13% vs. 56%, P<0.001). Echocardiography demonstrated progressive left ventricular (LV) dilatation and reduction in LV fractional shortening in male but much less marked changes in female TG mice. Incidences of atrial thrombosis, pleural effusion and lung congestion were higher and myocyte size and fibrosis in the LV were greater in TG males than females. Deprivation of testicular hormones by castration during 3-15 months of age improved survival and significantly ameliorated LV dysfunction, remodeling and hypertrophy compared with intact TG males. No significant effect, except for a trend of a better survival, was detected by ovariectomy in TG females. In conclusion, cardiac 2-AR overexpression at a high level leads to cardiomyopathy and heart failure with aging. Female mice had less cardiac remodeling, dysfunction and pathology and a marked survival advantage over male mice, and this was independent of prevailing levels of ovarian hormones. TG males showed benefit from orchiectomy suggesting a contribution by testicular hormones to the progression of the cardiomyopathic phenotype.
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